**Carotid Artery – Pathology, Plaque Structure – Relationship between Histological Assessment, Color Doppler Ultrasonography and Magnetic Resonance Imaging – Dolichoarteriopathies – Barorreceptors**

Ricardo Luis Beigelman, Andrés María Izaguirre, Francisco Azzato and José Milei

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/57157

**1. Introduction**

Carotid artery atherosclerosis is a major cause of disabling stroke and death [1] and it is thought to be the predominant etiology of stroke in Western society [2]. Moreover, stroke is the third leading cause of death and the primary cause of disability in the world [2].

Compared with medical therapy, surgical endarterectomy or carotid stenting have been proven to decrease stroke in symptomatic patients with severe stenosis[3-7] and in a very selective group of asymptomatic patients suffering of this pathology[8-9]

Nevertheless, clinical assessment of stroke risk had not progressed beyond the use of luminal stenosis in spite of evidence to suggest that this is an inadequate predictor of stroke. [10]

More recently, imaging studies have suggested plaque composition as an independent risk factor for ischemic stroke. [11]

Because of this, many efforts have been made to correlate symptoms and cerebral events with histological studies, color doppler ultrasonography (CDU) and magnetic resonance imaging (MRI).

Carotid dolichoarteriopathies were have also been proposed as a source of cerebral vascular insufficiency but this issue remains very controversial in the literature.[12-14]. In this chapter, our experience on CDU of neck vessels in 885 individuals with carotid dolichoarteriopathies

(age 1-day-old infants to 90-year-old adults),[15-16], the correlation of plaque appearance between B ultrasonography and pathology, [17] and the histological assessment in 281 carotid endarterectomy specimens [18] will be widely described and discussed.

**2. Pathology**

the dominant cells. [29]

carotid were involved.

and anti-CD34 was observed in all cases

Carotid atherosclerosis is commonly associated with symptoms of cerebral ischemia. However little attention has been directed to intraplaque factors that precipitate the onset of symptoms. [25] On the other hand, the treatment of coronary and carotid atherosclerosis, requires an understanding of the pathogenesis of plaque fissure. [26] Advances in molecular biology, coronary diagnostic techniques and cardiac treatments have suggested new factors leading to plaque fissure. [26-28] It was suggested that the risk of plaque fissure depends on plaque composition rather than plaque size, because only plaques rich in soft extracellular lipids are prone to rupture. [27] Also, it was demonstrated that ruptured plaque caps have much larger transverse gradients of connective tissue constituents than non-ruptured plaque caps, and that the development of these transverse gradients may be critical in determining the propensity of a plaque to rupture. [28] It was also shown that the site of rupture of thrombosed coronary atherosclerotic plaques is marked by an inflammatory infiltration where the macrophages are

Carotid Artery – Pathology, Plaque Structure – Relationship between Histological Assessment, Color Doppler...

http://dx.doi.org/10.5772/57157

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However, the exact mechanisms causing plaque rupture are yet not complete known. [29] In this connection, papers dealing with rupture of carotid plaque surface are few in spite of the growing importance of the subject. [18,19,30] We analyzed in pioneer papers[18,19,30] the cellular and vascular components of surgically excised carotid endarterectomies. Thus, the cell populations involved in the inflammatory activity in atherosclerotic lesions were further characterized with cell specific monoclonal antibodies in order to obtain information about their role in the pathogenesis of plaque rupture and intraplaque hemorrhage.[30] In brief, 76 surgical specimens of 74 patients who were submitted to carotid endarterectomy were used for these studies. There were 55 males and 19 females. Age ranged from 40 to 83 years (mean 69.4 years).Patients were divided into three clinical subgroups: asymptomatic (carotid lumen obstruction > 70%), symptomatic (stable) and symptomatic (unstable). The usual unifying pathologic feature in the plaques was the presence of large lipid cores with a fibrous cap overlying the lipid core and a band of fibrous tissue of varying thickness separating the plaque from the atrophic media (Figure 1). This collagen rim was in general extensively vascularized. Exceptionally the plaque was composed of fibrocellular tissue without a clear lipid core. In most cases, widespread chronic inflammatory infiltrates were observed either in the cap or in the lipid core (Figure 2). In all cases the carotid bifurcation and the first 1.5 cm of the internal

The result of immunophenotyping of the cellular constituents of the plaques were described in relation to the different layers (from the lumen to the media), namely: Endothelial lining (Anti-CD31 and anti-CD34). The fibrous cap at the site of the rupture/erosion had an eroded surface characterized by loss of the endothelial lining (Figure 3). On the other hand in the remaining surface a continuous, not damaged row of endothelial cells stained with anti-CD31

**Fibrous cap:** the collagenous fibrous cap at the site of erosion was attenuated and the pheno‐ typic characterization of the cells showed inflammatory components consisting mainly of macrophages (CD68 positive), approximately 2/3 of the total infiltration (Figure 4). The

In this connection, in a pioneer study we made a complete immunohistochemical characteri‐ zation in complicated carotid plaques. [18] The cellular components of carotid endarterectomy specimens were analyzed to assess their role in the pathogenesis of plaque rupture and intraplaque hemorrhage without rupture. The site of plaque rupture is associated with the presence of an extensive infiltrate of macrophages, T-lymphocytes, scarce B-lymphocytes, mast cells, and smooth muscle cells. Both the plaques showing these features and those with large amounts of lipid and thin fibrous caps, should be considered as "plaques at risk". Intraplaque hemorrhages without plaque rupture may be caused by the breakdown of neoformed vessels in the core, base, and periphery of the plaques. [18]

This paper emphasized the importance of the detection of vulnerable plaque for preventing future cerebral events. The main factors in advanced plaque that are most likely to lead to complications are the thickness of the fibrous cap, the size of the necrotic core and intraplaque hemorrhage, and the extent of inflammatory activity within the plaque.

Later on, we analyzed the relation between the anatomy of the carotid plaques and the presence of symptoms in 281 carotid endarterectomy specimens. [19] Almost 70% of plaque specimens demonstrated thrombus, intraplaque hemorrhage, or both. Thrombosis was observed in one fourth of specimens, and intraplaque hemorrhage in almost two thirds of specimens. Sixty four percent of plaques demonstrated neovascularization. In spite of findings in some published articles, [20] it was not possible to demonstrate that complicated plaques (plaque rupture, thrombosis, intraplaque hemorrhage) are associated with symptoms, and it appears that complicated plaques may occur at any time, irrespective of symptoms. [19]

Regarding the biology of the unstable atherosclerotic carotid plaque, an expression of c-fos, p53 and PCNA was demonstrated by us. [21]

On the other hand, MRI has excellent soft tissue contrast and is able to quantify carotid plaque size and composition with good accuracy and reproducibility and provides an opportunity to prospectively examine the relationship between plaque features and subsequent cerebrovas‐ cular events. [22] In a paper by Takaya et al [23] 154 patients with an asymptomatic 50% to 79% carotid stenosis by ultrasound with > or =12 months of follow-up were included for multicontrast-weighted carotid MRIs were included. Over a mean follow-up period of 38.2 months, arteries with thinned or ruptured fibrous caps, intraplaque hemorrhage, larger maximum %lipid-rich/necrotic cores, and larger maximum wall thickness were associated with the occurrence of subsequent cerebrovascular events. [23]

MRI imaging techniques have permitted serial monitoring of atherosclerotic disease evolution and the identification of intraplaque risk factors for accelerated progresión. [22]

At last, based upon our research, carotid barochemoreceptor involvement in old patients who died from stroke and suffering obstructive carotid atheromatosis will be discussed. [24]
